Abstract
Current treatment options for MPS I have limited effects on some organs, including the skeletal system. In MPS animal models pentosan polysulphate (PPS) reduces the concentrations of glycosaminoglycans (GAGs) in tissues and body fluids and improves cartilaginous and osseous pathologies. The goals of this study were to investigate primarily the safety and secondary the clinical effects, concerning mobility and pain, of PPS treatment in MPS I patients. Four MPS I-Hurler-Scheie/-Scheie patients aged 35.6 ± 6.4 years with one male were included in the study. All patients were on enzyme replacement therapy since 9.45 ± 3.75 years. PPS was applied subcutaneously in two patients with 1 mg/kg and in two patients with 2 mg/kg, weekly for 12 weeks and then biweekly for 12 weeks. The 24-week treatment with PPS was well tolerated by all patients. Urinary GAG concentrations were reduced from 4.13 ± 1.17 at baseline to 2.69 ± 0.36 mg/mmol creatinine after 24-week treatment with 1 mg/kg PPS, and from 6.71 ± 0.62 to 2.65 ± 0.09 mg/mmol creatinine with 2 mg/kg PPS. An improvement in range of motion was noted in three out of four patients. The pain intensity score was reduced from 4.5 ± 1.77 at baseline to 1.8 ± 0.47 after 24-week treatment with 1 mg/kg PPS; patients with 2 mg/kg PPS already had minimal pain at the start of the study. In conclusion, PPS treatment in a small number of adult MPS I patients was well tolerated and resulted in a significant reduction of urinary GAG excretion and in an improvement of joint mobility and pain.
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Acknowledgments
This study was supported by Multiplex Pharma Holdings, Miami Beach, FL, USA. We thank Klaus Marg, bene pharmaChem Geretsried/Germany, for its consultations.
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The study was supported by Multiplex Pharma Holdings, Miami Beach, FL, USA. Further on, Julia B. Hennermann had received speaker honoraria and travel support from Genzyme and Shire, as well as research/education grants from Shire. Seyfullah Gökce declares that he has no conflict of interest. Alexander Solyom received payment for consultations from Plexcera Therapeutics LLC. Eugen Mengel had received speaker honoraria and travel support from Genzyme and Shire, grants from Genzyme, and consultation fees from Biomarin. Edward H. Schuchman and Calogera M. Simonaro are co-inventor’s on a patent, “Anti-TNF therapy for the mucopolysaccharidoses and other lysosomal storage diseases”, that has been awarded to the Icahn School of Medicine at Mount Sinai and licensed to Plexcera Therapeutics. Edward H. Schuchman is a co-founder and equity owner of Plexcera Therapeutics. Calogera M. Simonaro is a consultant to Plexcera Therapeutics. This does not alter the authors’ adherence to all JIMD policies on sharing data and materials.
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All procedures followed were in accordance with the ethical standards of the responsible institutional committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.
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Communicated by: Olaf Bodamer
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Supplementary Table 1
Overview of all adverse events reported during treatment of MPS I patients with PPS in different doses of 1–2 mg/kg. (DOCX 18 kb)
Supplementary Fig. 1
Flow diagram of the trial, indicating the number of included, treated and analyzed patients (DOC 30 kb)
Supplementary Fig. 2
Individual concentrations of aPTT of the patients during the trial and the treatment with PPS. aPTT concentrations were always measured pre dosing and two hours post dosing. During V1-14 PPS was applied weekly, during V14-V20 biweekly. LR, lower range; UR, upper range (GIF 200 kb)
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Hennermann, J.B., Gökce, S., Solyom, A. et al. Treatment with pentosan polysulphate in patients with MPS I: results from an open label, randomized, monocentric phase II study. J Inherit Metab Dis 39, 831–837 (2016). https://doi.org/10.1007/s10545-016-9974-5
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DOI: https://doi.org/10.1007/s10545-016-9974-5